For the purpose of preparing oligodeoxynucleotides, there have widely been used two processes, called phosphate triester process and phosphite triester process. In the phosphate triester process, a deoxynucleoside-3'-phosphate compound of general formula (A) shown below is usually used as an intermediate compound. The phosphite triester process, on the other hand, usually uses as an intermediate compound either a deoxynucleoside-3'-O-phosphorchloride compound of general formula (B) or a deoxynucleoside-3'-O-phosphoramidite compound of general formula (C) given below. ##STR2## wherein R is a hydroxy-protecting group, R' is a phosphate- or phosphite-protecting group, R" is an alkyl group and B is a base residue which may have a protecting group. Details on the preparation and uses of compounds (A) are described in C. B. Reese, Tetrahedron, 34, 3143 (1978), those of compounds (B) are in R. L. Letsinger et al., J. Am. Chem. Soc., 97, 3278 (1975) and those of compounds (C) are in M. H. Caruthers et al., Tetrahedron Lett. 22, 1859 (1981), all the disclosures of which are incorporated by reference herein.
Main advantage of the phosphate triester process is in that compounds (A) are stable against oxygen and water with the ease in the preparation and handling thereof. This will be a primary reason why the said process has prevailingly been adopted for practical applications. However, the phosphate triester process has such inconvenience that the condensation reaction of a compound (A) with a 5'-O-deoxynucleoside or a 5'-O-deoxynucleotide, so-called internucleotide-forming reaction, is not so fast as desired, requiring a relatively long time to obtain oligomers intended.
On the other hand, the phosphite triester process wherein compounds (B) or (C) are used has an advantage that both compounds (B) and (C) exhibit high reactivities on the alcoholic hydroxyl group of 5'-O-deoxynucleosides or 5'-O-deoxynucleotides, thus can bring a rapid internucleotide-forming reaction to afford desired oligodeoxynucleotide product with much less reaction time than that required in the phosphate triester process. In particular, the phosphite triester process is effectively applicable to solid phase processes for the preparation of oligodeoxynucleotides. However, compounds (B) and (C), particularly compounds (B), have such drawbacks that their preparation and handling are not simple or easy, that they are unstable to oxygen and water, so that care must be taken to avoid their decomposition during storage and use, and the like. In fact, it is known that compounds (B) are generally so unstable as to be difficult to isolate them from the reaction system in their preparation and that compounds (C) are also unstable to such extent that their P-N bond is readily severed even in the presence of a weak acid.
In the light of the level of the prior art as explained above, we have investigated on the preparation of oligodeoxynucleotides with the main intention of looking for useful intermediate compounds therefor in the sense that they can easily be prepared, are stable under storage and convertible readily and rapidly to desired oligodeoxynucleotides and have now synthesized, for the first time, phosphorsulfide derivatives of deoxynucleosides and of deoxynucleotides of the structure hereinafter specified which are advantageously adaptable for the purpose as intended above.